Mineralocorticoid regulation of epithelial Na+ channels is maintained in a mouse model of Liddle's syndrome

Am J Physiol Renal Physiol. 2003 Aug;285(2):F310-8. doi: 10.1152/ajprenal.00016.2003. Epub 2003 Apr 8.


Currents through epithelial Na channels (ENaCs) were measured in the cortical collecting tubule (CCT) of mice expressing truncated beta-subunits of ENaC, reproducing one of the mutations found in human patients with Liddle's syndrome. Tubules were isolated from mice homozygous for the Liddle mutation (L/L) and from wild-type (WT) littermates. Amiloride-sensitive currents (INa) from single cells were recorded under whole cell clamp conditions. CCTs from mice kept under control conditions and fed a diet with normal levels of Na had very small INas (WT: 18 +/- 13 pA; L/L: 22 +/- 8 pA at Vm = -100 mV) that were not different in WT and L/L animals. However, the L/L mice had much larger currents when the animals were fed a low-Na diet (WT: 256 +/- 127 pA; L/L: 1,820 +/- 330 pA) or infused with aldosterone (WT: 285 +/- 63 pA; L/L: 1,600 +/- 280 pA). Currents from L/L mice were also larger when animals were pretreated with a high-K diet but not when the CCTs were stimulated in vitro with 8-CTP-cAMP. Noise analysis of amiloride-induced fluctuations in INa showed that single-channel currents at Vm = 0 mV were slightly smaller in L/L mice (WT: 0.33 pA; L/L: 0.24 pA). This difference could be attributed to a decrease in driving force since current-voltage analysis indicated that intracellular Na was increased in the L/L animals. Analysis of spontaneous channel noise indicated that the open probability was similar in the two genotypes(WT: 0.77; L/L: 0.80). Thus the increase in whole cell current is attributed to a difference in the density of conducting channels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldosterone / pharmacology*
  • Amiloride / pharmacology
  • Animals
  • Disease Models, Animal
  • Diuretics / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Sodium Channels
  • Hypertension / genetics
  • Hypertension / metabolism*
  • Kidney / drug effects
  • Kidney / metabolism*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Models, Biological
  • Patch-Clamp Techniques
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Sodium, Dietary / pharmacokinetics


  • Diuretics
  • Epithelial Sodium Channels
  • Sodium Channels
  • Sodium, Dietary
  • Aldosterone
  • Amiloride